Novel PET imaging method more fully evaluates extent of rheumatoid arthritis inflammation

July 9, 2018, Society of Nuclear Medicine and Molecular Imaging
CT and 11C-PBR28 PET SUV images of both knees of (i) an RA patient with clinical signs of synovitis both knees, and (ii) a healthy control. Credit: N Narayan et al. 2018, University of Oxford, Headington, Oxford, UK

A new positron emission tomography (PET) imaging method more fully evaluates the extent of rheumatoid arthritis by targeting translocator protein (TSPO) expression in the synovium (joint lining tissue). The study is featured in the July issue of The Journal of Nuclear Medicine.

PET radioligands that target TSPO, which is highly expressed on activated (immune cells responding to inflammation), have proved an excellent tool for imaging joint inflammation in rheumatoid arthritis (RA).

"TSPO-targeted imaging has long been used as a means of imaging macrophage infiltration in vivo," explains Nehal Narayan of the University of Oxford in Oxford, U.K. "Numerous studies have demonstrated TSPO-targeted PET as a highly sensitive and specific means of imaging synovitis [inflammation of joint lining tissue], purportedly through imaging synovial macrophage infiltration, a critical process in RA pathogenesis. However, this premise does not take into account the ubiquitous expression of TSPO."

She points out, "Here we present the first ever analysis of TSPO expression in the major constituents of RA pannus (inflamed synovium), demonstrating that TSPO PET likely acts as an imaging tool of not only macrophages, but also activated synovial fibroblasts, a cell group increasingly recognised to play a critical role in RA inflammation."

The study included three RA patients and three healthy volunteers who underwent PET scans of both knees using the TSPO radioligand carbon-11 (11C)-PBR28. In addition, cellular expression of TSPO was examined in synovial tissue from these individuals, plus three more RA patients and three more healthy patients (undergoing knee arthroscopy for injuries). TSPO mRNA expression and hydrogen-3 (3H)-PBR28 radioligand binding were assessed using in vitro monocytes, macrophages, fibroblast-like synoviocytes (FLS) and CD4+ T-lymphocytes.

Results showed that the 11C-PBR28 PET signal was significantly higher in RA joints compared to healthy joints. In addition, 3H-PBR28 specific binding in synovial tissue was approximately 10-fold higher in RA patients compared to healthy controls. Immunofluorescence revealed TSPO expression on macrophages, FLS and CD4+ T cells. In vitro study demonstrated highest TSPO mRNA expression and 3H-PBR28 specific binding in activated FLS, non-activated and activated 'M2' reparative macrophages. The lowest TSPO expression was in activated and non-activated CD4+ T lymphocytes.

Narayan notes, "It is well recognised that not all currently available treatments are capable of controlling joint inflammation in all patients with , hence the need to develop new pharmacological therapies. This work demonstrates that TSPO PET is able to act as a means of imaging not only synovial macrophages, but also activated synovial fibroblasts. The crucial role of the fibroblast and its soluble products in RA pathogenesis is increasingly realised."

She adds, "Indeed, there has been recent interest in targeting activated fibroblasts as a novel targeted treatment strategy for RA. Therefore, TSPO PET imaging in early phase clinical trials may provide a sensitive indication of treatment response to such novel therapies with a view to informing the design of later stage clinical trials. As our knowledge of cellular TSPO and behavior grows, TSPO-targeted imaging may also give us unique insights into the pathogenesis of inflammatory disease."

Explore further: PET imaging agent could provide early diagnosis of rheumatoid arthritis

More information: Nehal Narayan et al, Translocator Protein as an Imaging Marker of Macrophage and Stromal Activation in Rheumatoid Arthritis Pannus, Journal of Nuclear Medicine (2018). DOI: 10.2967/jnumed.117.202200

Related Stories

PET imaging agent could provide early diagnosis of rheumatoid arthritis

May 3, 2018
A novel PET tracer developed by Korean researchers can visualize joint inflammation and could provide early diagnosis of rheumatoid arthritis, a common autoimmune disease that causes chronic inflammation of joints and can ...

Brain is susceptible to acute MI, chronic heart failure

January 17, 2018
(HealthDay)—Acute myocardial infarction (MI) and chronic heart failure have effects on the brain, according to a study published in the Jan. 23 issue of the Journal of the American College of Cardiology.

Over years, depression changes the brain, new study shows

February 27, 2018
Is clinical depression always the same illness, or does it change over time?

Drugs found to both prevent and treat Alzheimer's disease in mice

May 21, 2013
Researchers at USC have found that a class of pharmaceuticals can both prevent and treat Alzheimer's Disease in mice.

Brain biomarker shows promise in heart

January 27, 2014
A biomarker widely used to diagnose brain injury has shown early promise for assessing the severity of heart inflammation, or myocarditis, find researchers at Columbia University's Mailman School of Public Health, Johns Hopkins, ...

Imaging study finds first evidence of neuroinflammation in brains of chronic pain patients

January 12, 2015
A new study from Massachusetts General Hospital (MGH) investigators has found, for the first time, evidence of neuroinflammation in key regions of the brains of patients with chronic pain. By showing that levels of an inflammation-linked ...

Recommended for you

Dietary carbohydrates could lead to osteoarthritis, new study finds

August 9, 2018
Do your knees ache? According to new findings from the Oklahoma Medical Research Foundation, your diet could be a culprit.

Joint study raises questions about treatments for arthritis

August 3, 2018
A study examining how molecules are transported into knee-joint tissue could have major implications for understanding and treating arthritis.

Researchers identify new arthritis severity gene

July 26, 2018
A new gene associated with disease severity in models of rheumatoid arthritis has been identified by researchers at the Icahn School of Medicine at Mount Sinai. The discovery could provide a new pathway for treatment and ...

How the brain plays a role in rheumatoid arthritis inflammation

June 18, 2018
In patients with chronic inflammatory conditions, such as rheumatoid arthritis, there has been limited understanding of how this inflammation affects the brain.

New 3-D imaging analysis technique could lead to improved arthritis treatment

June 18, 2018
An algorithm to monitor the joints of patients with arthritis, which could change the way that the severity of the condition is assessed, has been developed by a team of engineers, physicians and radiologists led by the University ...

Joint resolution: A link between Huntington's disease and rheumatoid arthritis

May 15, 2018
Using new analytic tools, researchers at University of California San Diego School of Medicine and the Icahn School of Medicine at Mount Sinai have decoded the epigenetic landscape for rheumatoid arthritis (RA), a common ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.